What is neuropathic pain?
Neuropathic pain, for example in diabetic neuropathy or post-herpetic neuralgia, often does not respond to normal analgesics. It is usually treated with anti-epileptic drugs or antidepressants which, however, have many side effects. Recently, there are indications that morphine mimetics such as tramadol are also effective and have fewer side effects. Aim To assess the effectiveness of tramadol in the treatment of neuropathic pain. Search strategy and outcomes With an extensive search strategy using the usual Cochrane method, the review included all randomized and quasi-randomized controlled trials comparing tramadol with placebo, another pain relieving treatment or no treatment – regardless of gender, age, cause or severity of the pain. The outcome measure was the number of patients whose pain decreased by at least 50% according to their own reports or according to a score on a validated pain scale. Results Five trials were found. Two compared tramadol (in doses ranging from 100 to 400 mg per day) with a placebo in a total of 166 patients with diabetic neuropathy. A cross-oversial compared tramadol with a placebo in 45 patients with unspecified neuropathic pain. All these patients were allowed to use paracetamol; this was done significantly more frequently during placebo use than during tramadol use.
One trial compared tramadol with clomipramine in 21 patients with postherpetic neuralgia. This trial was not double-blind. Finally, there was a trial comparing tramadol with morphine in 40 patients with cancer who had an unknown number of neuropathic pain. No conclusions could be attached to this last trial for that reason. The dropout during the trials was substantial. Of the 131 patients with diabetic neuropathy from the first trial, 22 (34%) were in the tramadol group and 27 (41%) in the placebo group, mainly due to a lack of effect. The dropout in the other trial with diabetes patients is not known. At the cross-outset, 8 patients (18%) dropped out during tramadol use and 3 (7%) during placebo use, mostly due to side effects. Of the 35 patients with post-herpetic pain, 14 (40%) were excluded due to side effects, as much in tramadol as in clomipramine. The effectiveness with respect to clomipramine could not be determined on the basis of this one trial because the number of patients was too small; there was no difference in effectiveness in the trial. The conclusions are based on the 3 trials with placebo. In order to achieve 50% pain relief in 1 patient, 3.5 patients must be treated with tramadol. Tramadol is thus significantly more effective than a placebo and about as effective as the traditionally used agents (NNT 2.4 for tricyclic antidepressants, 2.5 for carbamazepine and 3.7 for gabapentin). Out of every 7.7 patients treated with tramadol, 1 gets so many side effects that it stops the treatment. There were no life-threatening side effects during tramadol use in these trials. Conclusion The authors conclude that tramadol is an effective treatment for neuropathic pain, with reversible side effects. The effectiveness seems similar to that of antidepressants and anticonvulsants, but adequate direct comparisons are not available.
Few trials with a lot of dropout, no conclusive comparison with traditional means, no comparison with other analgesics and an author who is also an advisor to the company that produces tramadol: it does not make a strong convincing impression. On the other hand, antidepressants and anticonvulsants often have many side effects and a disappointing effect in practice. Most general practitioners will usually start with a familiar remedy for pain of any kind with relatively few side effects, even though they know that other drugs are recommended for neuropathic pain. With this review in mind, they can feel empowered in this approach, and certainly try tramadol in patients with neuropathic pain.